Urology News and Education Resource
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Friday, 29 March 2024 |
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UroToday is honored to introduce Petros Grivas, MD, PhD, Editor-in-Chief of the The Advanced Bladder Cancer Center of Excellence. Over the past three years we have seen notable changes in the treatment of advanced bladder cancer. The advent of immune checkpoint inhibitors (ICI) has heralded a new era after approximately two decades of a “stagnant landscape”. The mission of this Center is providing a resource of current information for clinical-decision making in this dynamic environment. At the era of next-generation sequencing and the report of ’The Cancer Genome Atlas Project”, there has been renewed interest in the field of targeted therapies, which have encountered significant challenges due to tumor heterogeneity, genomic instability and clonal evolution. The recent development of new agents and companion diagnostic assays signaled a new age of experimental therapeutics in urothelial carcinoma. As a result, the first targeted therapy for this cancer was approved by the FDA on April 12, 2019. Erdafitinib, an orally available pan-FGFR inhibitor, received accelerated approval based on impressive overall response rate and acceptable toxicity profile noted in a phase II trial in patients with metastatic bladder cancer harboring Fibroblast Growth Factor Receptor 2/3 (FGFR 2/3) genomic alterations noted on a companion diagnostic assay (RT-PCR by Qiagen). Welcome to this center of excellence where improving the quality of life of our advanced bladder cancer patients is central to our objectives.
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From the Desk of the Editor, Welcome to the Advanced Bladder Cancer Center of Excellence
Petros Grivas, MD
Bladder cancer is common and challenging to treat. Thorough assessment of the molecular biology and immunology background has pinpointed potential biomarkers, “drivers” and promising therapeutic targets. The advent of immune checkpoint inhibitors (ICI) has heralded a new era after approximately two decades of a “stagnant landscape”. As single agents in patients with advanced urothelial carcinoma, ICI can induce rapid and durable responses, with a very small proportion of patients achieving long term remission. However, most patients do not achieve response, while a proportion may have immune-related adverse events. Therefore, there is an urgent need for additional therapies that raise the bar, improve quality of life, and further prolong the life of our patients.
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Results from CALGB 90601 in Metastatic Urothelial Carcinoma
Jonathan Rosenberg, MD
Jonathan Rosenberg, MD, discusses results presented of "Randomized, Double-Blind, Placebo-Controlled Phase III Trial Comparing Gemcitabine and Cisplatin with Bevacizumab or Placebo in Patients with Metastatic Urothelial Carcinoma — CALGB 90601" (Alliance). Dr. Rosenberg confirms that the addition of bevacizumab did not improve overall survival when added to gemcitabine and cisplatin chemotherapy as first-line therapy for metastatic urothelial carcinoma.
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Erdafitinib in Bladder Cancer
Arjun V. Balar, MD
FGFR alterations and specifically ones involving the third and the second isotype of the receptor, FGFR3 and FGFR2, are activated and present in between 15 to 20%, possibly higher, of patients with locally advanced and metastatic bladder cancer. We know that these are genetic drivers and the therapeutic targeting of this pathway can lead to responses. Patients should be selected for therapy based on an FDA-approved companion diagnostic for erdafitinib.
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Advances in Bladder Cancer Beyond Immunotherapy and Checkpoint Inhibitors
Evan Yu, MD
Evan Yu and Alicia Morgans have a diverse conversation highlighting the advances in the field of bladder cancer beyond IO and Checkpoint inhibition. They introduce a variety of therapy options being studied such as FGFR inhibition, antibody-drug conjugates, HER-2 and DNA repair.
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EV-201: Results of Enfortumab Vedotin Monotherapy for Locally Advanced or Metastatic Urothelial Cancer Previously Treated with Platinum and Immune Checkpoint Inhibitors
Daniel Petrylak, MD presented results of first phase study of antibody drug conjugate Enfortumab Vedotin (EV) for the treatment of locally advanced or mUC. EV shows promising antitumor activity for high risk population. In this study, the authors describe the results of EV-201, EV monotherapy for locally advanced or metastatic urothelial cancer previously treated with platinum and immune checkpoint inhibitors.
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FIERCE-22: Clinical Activity of Vofatamab - FGFR3 Selective Inhibitor in Combination with Pembrolizumab in WT Metastatic Urothelial Carcinoma
FGF receptor 3 (FGFR3) alterations are frequently encountered in urothelial carcinoma, both in non-muscle invasive and muscle-invasive disease. Early studies suggest that patients with pathogenic FGFR do not respond to immune checkpoint inhibition. This abstract provides data on 28 patients with mUC who had progressed on at least 1 line of prior therapy.
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Phase II Study of Nivolumab and Ipilimumab for Advanced Bladder Cancer of Variant Histologies
In urothelial carcinoma, CheckMate 032 evaluated the efficacy of ipi/nivo in an open-label, multicenter, phase I/II study. Patients were eligible if they had progressed on one or more prior lines of platinum-based chemotherapy and the primary endpoint was an objective response rate by RECIST 1.1. For patients with non-urothelial bladder cancer, it is unknown if ipi/nivo is effective. This study evaluates nivo and ipi for advanced bladder cancer of variant histologies.
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An Update on Muscle Invasive Bladder Cancer and Metastatic Bladder Cancer
Bladder cancer was one of the top five leading causes of cancer death in 2015. Most of these cases are of urothelial histologic origin. For about 35% of patients, bladder cancer is either muscle-invasive or metastatic at disease presentation. In addition, non-muscle invasive disease can progress to become muscle-invasive bladder cancer later on in the disease course. Preceding chapters discussed the diagnosis and staging of bladder cancer. This chapter will focus on the management of muscle-invasive urothelial bladder cancer as well as metastatic bladder cancer.
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Immuno-Oncology: The Urologist's Role
After decades of relative stagnation, patients with urothelial carcinoma are receiving approved immuno-oncologic drugs that significantly extend survival and are safer and more tolerable than chemotherapy. The success of these treatments in metastatic bladder cancer has generated strong interest and promising early results for their use in localized disease. Noah Hahn, MD discusses Immuno-oncology and the urologists role that comes with.
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A Phase II Study of RC48-ADC in HER2-Positive Patients with Locally Advanced or Metastatic Urothelial Carcinoma
Antibody-drug conjugates (ADCs) have made significant progress in several tumor types over the past few years. Linking a targeted monoclonal antibody to a drug allows for increased specificity of drug delivery, potentially sparing normal tissue from toxicity and optimizing drug release strategies by forcing intracellular accumulation of released drug in antigen-positive cells. This study was conducted to further analyze the response of RC48 for HER2+ mUC.
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